Human papillomaviruses (HPVs) represent some of the most common of the sexually transmitted diseases. More than 70 HPV types have been identified, and some types have been strongly implicated as causative agents in the onset of cervical, vaginal, penile and skin cancers. Microbicides as anti-papillomavirus agents have not been described. Recently, several in vitro papillomavirus infectivity models have been documented that make feasible the screening of microbicides for potential anti-papillomavirus activity. Our long term goal is to establish the validity of three papillomavirus in vitro infectivity models for testing anti-papillomavirus formulations. The models we propose to use are (i) BPV-1 induced focus-formation of mouse C127 cells, (ii) transient infection of rabbit cell lines Sf1Ep and RK-13 with CRPV, and (iii) infection of human foreskin chips with HPV-11 prior to grafting into the renal capsule of athymic mice. We have established that neutralizing monoclonal antibodies (N-MAbs) can operate as effective anti- papillomavirus reagents in each of these three model systems, and thus provide the only positive control anti-virucide known for these viruses. The N-MAbs showed that in all three in vitro systems there were similar kinetics of virus binding and internalization, suggesting that all three models describe a common mechanism of infectivity. We will combine the results of screening in the in vitro assay systems with a novel human vaginal xenograft model that will be infected with HPV-11 (described in Project #1, Dr. John Kreider, Project leader) to confirm the effectiveness of anti-papillomavirus formulations.